Neural interface insertion and retraction tools

ABSTRACT

Devices and methods for manipulating devices such as micro-scale devices are provided. The devices can include a tether of various materials surrounded by a stiff body. The tether interfaces with microscale devices to draw them against the stiff body, holding the microscale devices in a locked position for insertion into or extraction out of tissue. The tensional hook and stiff body are configurable in a multitude of positions and geometries to provide increased engagement. Such configurations allow for a range of implantation and extraction surgical procedures for the device within research and clinical settings.

STATEMENT REGARDING FEDERALLY SPONSORED R&D

This invention was made with government support under NIH Grant/FederalIdentifier Number R43NS081837 awarded by the National Institutes ofHealth of the United States of America. The government may have certainrights in the invention.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication are hereby incorporated by reference under 37 CFR 1.57.

BACKGROUND

Some aspects of the present invention relates generally to tools used toimplant and remove neural interface devices within nervous systems. Moreparticularly, some embodiments of the invention relates to devicesystems that can be used to insert and retract a range of microscaledevices dependent upon the desired research or clinical purpose.

SUMMARY

Disclosed herein is a method of inserting a micro-scale device into atarget substrate. The method can include, in some embodiments, providingan insertion tool comprising a tether having a proximal end, a distalend, and an elongate body, and an end effector operably connected to thedistal end of the tether. The method can also include mechanicallycoupling the end effector to a portion of the micro-scale device. Themethod can also include positioning the micro-scale device at a desiredlocation within a target substrate. The method can further includemechanically decoupling the end effector from the micro-scale device.Also, the method can include withdrawing the insertion tool from thetarget substrate. In some embodiments, positioning the micro-scaledevice at a desired location includes moving the end effector distallywith respect to a housing of the insertion tool. The housing caninclude, for example, a tubular body that includes a central lumen. Theend effector can include a hook on its distal end, and/or a releasableconnector. At smaller scales, the end effector can be pushed like a rodand pulled in tension like a cable. The micro-scale device can include,for example, a neural and/or biological interface.

In some embodiments, mechanically coupling the end effector to a portionof the micro-scale device can include positioning the hook through anaperture, hook-like structure, or other complementary element on themicro-scale device. Mechanically decoupling the end effector to aportion of the micro-scale device can include disassociating the hookfrom an aperture on the micro-scale device. In some embodiments, thetarget substrate is non-stationary, and can include neural tissue. Insome embodiments, mechanically coupling the end effector to a portion ofthe micro-scale device does not substantially displace the micro-scaledevice.

The method can also include, in some embodiments, monitoring the motionof the nonstationary target surface. Positioning the micro-scale devicecan also include adjusting the positioning speed as a function of themonitored motion of the target surface. Positioning can also includemanipulating a tab on the end effector. In some embodiments, positioningthe micro-scale device comprises actuating a control on the proximal endof the device to move the tether with respect to the elongate body.Actuating a control can also include rotating a control knob in adirection, thereby moving a tracking pin axially distally within a slotoriented substantially parallel to the longitudinal axis of the elongatebody. The tether can be elastic or inelastic, and the sidewall of theaperture can be elastic in some embodiments.

In some embodiments, disclosed is a tool configured for inserting andretracting a micro-scale device. The tool can include one or more of ahousing, a tether including a proximal end, a distal end, and anelongate body. A portion of the tether can be configured to extenddistally from the housing in a first configuration and be retractedwithin the housing in a second configuration. The tool can also includean end effector operably connected to the distal end of the tether, theend effector configured to reversibly mechanically couple with a portionof the micro-scale device. The tool can be configured such that themechanical coupling does not substantially displace the micro-scaledevice. The housing can include a tubular body. The tether is configuredto slide within a channel of the housing. The end effector can include,in some cases, a hook, and a pivoting joint connected to the hook. Theend effector can also include one, two, or more laterally-extending tabsconfigured to allow a user to position the micro-scale device within atarget location. The end effector can also include an aperture near aproximal end of the end effector. The aperture can be configured tohouse a portion of the tether therethrough, thereby coupling the endeffector and the tether. In some embodiments, the tubular body caninclude a slot oriented axially with respect to a longitudinal axis ofthe tubular body. The tool can be configured to insert and retract aneural array. The end effector can also be threaded through an apertureon a micro-scale device. In some embodiments, the proximal end of thehousing can include a control knob operably connected to and configuredto actuate the tether proximally or distally with respect to thehousing. The tool can also include a slot on the housing, and can beoriented substantially parallel to a longitudinal axis of the housing.The tool can also include a pin oriented axially or radially on an innermember, such as an inner tubular member, and configured to slide in adirection, such as axially, with respect to the housing. The pin can beconfigured to move axially within the slot. The tether can be elastic orinelastic.

In some embodiments, disclosed herein is a neural interface deliverysystem, including an insertion and removal tool, and a neural interfaceand/or biological interface. In some embodiments, the neural microarraycan include a flexible baseplate, at least one microelectrode, and aloop on the flexible baseplate configured to reversibly couple with theend effector of the insertion and removal tool.

Also disclosed herein is a method of removing a micro-scale device froma target substrate. The method can include, for example, providing anremoval tool comprising a tether having a proximal end, a distal end,and an elongate body, and an end effector operably connected to thedistal end of the tether; mechanically coupling the end effector to aportion of the micro-scale device embedded at least partially within thetarget substrate; and withdrawing the insertion tool and the micro-scaledevice from the target substrate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an isometric view of an insertion device and a detail viewof a control knob mechanism, according to some embodiments of theinvention.

FIG. 1A shows an isometric view of an insertion device positioned abovea micro-scale device with an engagement hook extended, according to someembodiments of the invention.

FIG. 1B shows an isometric view of an insertion device with anengagement hook and a distal end engaged with a micro-scale device,according to some embodiments of the invention.

FIG. 1C shows an isometric view of an insertion device with anengagement hook and a distal end engaged with a micro-scale deviceinserted into tissue, according to some embodiments of the invention.

FIG. 1D shows an isometric view of tweezers displacing an engagementhook from the engagement loop of a micro-scale device, according to someembodiments of the invention.

FIG. 1E shows an isometric view of an insertion device retracted awayfrom a micro-scale device, according to some embodiments of theinvention.

FIG. 2 shows a side view of an insertion device with an adjustable hookabove a micro-scale device, according to some embodiments of theinvention.

FIG. 2A shows a side view of an insertion device with an adjustable hookengaged with a micro-scale device, according to some embodiments of theinvention.

FIG. 2B shows a side view of an insertion device with an adjustable hooktensioning a micro-scale device against the distal end of the insertiondevice, according to some embodiments of the invention.

FIG. 3 shows a side view of an insertion device with an extendedengagement hook above a micro-scale device with a flexible hingedbackplate, according to some embodiments of the invention.

FIG. 3A shows a side view of an insertion device with tweezersdisplacing an extended engagement hook, according to some embodiments ofthe invention.

FIG. 3B shows a side view of an insertion device with an engagement hooktensioning a micro-scale device with a flexible hinged backplate againstthe distal end of the insertion device, according to some embodiments ofthe invention.

DETAILED DESCRIPTION

Neural interfaces are implanted within the nervous systems of animalsand humans to record, stimulate, and treat neural tissue activity.Typically, this occurs within animal research of a variety of fields(e.g. neurological disorders and basic nervous system function) as wellas clinical diagnosis and therapy (e.g., epilepsy).

Neural interfaces are implanted through a variety of methods, and areheld during insertion by a variety of means including vacuum, mechanicallock, adhesive, dissolvable adhesive, and momentary impulse contact. Themost pervasive form of holding microscale devices for insertion is astiff engagement of some kind with a separate device such as amicro-positioner. It can be advantageous as it keeps delicate microscaledevices stiff during insertion into dynamic tissue and allows a range ofinsertion speeds. Impulse insertion is also popular for microscaledevices with large number of shanks. Impulse inserters are most commonlyformed from metal and polymer components and powered using pneumatics.The procedure of impulse insertion positions a cabled microscale deviceover targeted tissue. The impulse inserter is then placed over themicroscale device. The impulse inserter then receives a pneumatic pulsethat actuates the insertion mechanism, striking the microscale device ata high rate of speed and sending it into the neural tissue.

Unfortunately, the impulse process requires a high degree of skill toposition the microscale device and impulse inserter as well as actuatethe inserter at the appropriate time. The average researcher isincapable of using the technique without significant training and oftenrelies on an outsider with special expertise in impulse insertion.Mechanically locked insertion is a poor solution for implantingmicroscale devices for chronic experiments or periods. Microscaledevices meant for chronic implantation often have cables to implantedstructures. These cables are both delicate and resilient; they are easyto plastically deform to the point of damage, and if deflected too farduring insertion can apply a residual force on the implanted microscaledevice, resulting in damage to tissue over time. Basic assembly tomicroscale devices with cables is also challenging during surgeries asthe cables leading out of microscale devices terminate in largeconnectors which are affixed to tissue; the microscale devices are thenadjusted with small deflections of the cable until positioned over thetarget tissue. This process leaves little room for additional deflectionof the cable, increasing the requirement for flexibility of theinsertion device or insertion technique.

These limitations prevent the implantation of chronic neural interfacesin a wide variety of situations. This reduces the amount of dataacquired as well as limiting current and future therapies. Currentinsertion techniques also limit the visibility of the electrode for theresearcher.

Accordingly, in some embodiments, disclosed herein is an insertion andextraction device that manipulates micro-scale devices, and providesunlimited degrees of freedom for placing and removing micro-scaledevices. In some embodiments, the insertion and extraction device mayhave a tensional hook for engaging with micro-scale devices. It can alsobe advantageous to have a tensional loop. By using a loop, thecorresponding hook on an implanted micro-scale device might be easier toextract after a lengthy implantation that encapsulated the device intissue. In some embodiments, the insertion and/or retraction device mayhave a spring and dampening system to compensate for deflection oftissue during respiration. In other embodiments, the insertion and/orretraction device is actively positioned to follow the motion of tissue.In some embodiments, the insertion and/or retraction device uses acomputer to monitor the motion of the tissue and adjusts the speed anddeflection of the mechanical device accordingly within a closed loopfeedback system.

An insertion and/or retraction device capable of interfacing with aflexible baseplate (e.g., joining body) can also be advantageous in someembodiments as it allows customization of placement within the nervoussystem and increased conformity to anatomical variations for researchand clinical applications. In some embodiments, the joining body isconfigured to be flexible enough to bend around the outer curvature ofneural tissue (e.g., sulcus surface of cortex, circumference of a nerve,or surface of a plexus). In some embodiments the joining body isconfigured to be flexible enough to bend with the motion of neuraltissue due to respiration or containing body acceleration anddeceleration.

In some embodiments, disclosed herein is an insertion and/or retractiondevice to manipulate various devices, including but not limited toimplantable medical devices. The device to be inserted and/or removedcan be a micro-scale device in some embodiments, but is not necessarilylimited to devices to be inserted and/or retracted of a particular size.In some embodiments, the devices to be inserted and/or removed withsystems and methods as disclosed herein can have a device total volumeof about or less than about, for example, 100 mm³, 50 mm³, 25 mm³, 10mm³, 5 mm³, 2 mm³, 1 mm³, 0.5 mm³, 0.25 mm³, 0.1 mm³, 0.05 mm³, or less.In some embodiments. the device to be inserted and/or removed could be,for example, an implantable neural interface device. In someembodiments, the device to be inserted has dimensions of about 1 mm×1mm×1 mm or smaller. Neural interface devices as referred to herein couldinvolve brain or spinal cord devices, but also peripheral nerve devicesincluding sympathetic and parasympathetic nerves, as well as devicesthat monitor and/or treat cardiac and other tissues. The insertionand/or retraction device can interface with various types of micro-scaledevices, including but not limited to neural interfaces that act asrecording or stimulation electrodes, optical fibers, or as hollow tubesfor media, e.g., fluid delivery. In other embodiments, the insertionand/or retraction device can interface with biological sensors orstimulators for placement within organisms. In still other embodiments,the insertion and/or retraction device can interface with sensors orstimulators for placement within organisms. In some embodiments, theinsertion and/or retraction device can interface with micro-scaledevices for placement within movably positioned sheets, gels, foams,liquids, soil, artificial organisms, organic material, composites,mixtures, and other shapes of substrate. In other embodiments, the bodyof the insertion and/or retraction device can be shaped intoadvantageous configurations for manipulation and various treatmentmodalities including recording, stimulating, magnetic stimulation,magnetic monitoring, fluid delivery, temperature control, opticalstimulation, optical monitoring, video monitoring, and chemicalirrigation of neural tissue. In some embodiments, the body that includesthe tether could also serve as a delivery device for a drug, such as anantithrombotic agent, an antibiotic, an anti-inflammatory, ananti-epileptic, viral vectors, or a chemotherapeutic agent, for example.In some embodiments, the insertion and/or retraction device can place animplantable neural or non-neural interface device within any tissuewithin the body dependent upon the desired research or clinical result;including nervous, muscle, connective, epithelial, cardiac, lung, renal,gastrointestinal, and bone tissues. In some embodiments, the tissue is abody lumen, such as within a lumen or luminal wall of an artery or veinfor example. In some embodiments, the tissue is not within a lumenand/or luminal wall. In some embodiments, an insertion device can alsobe used as a retraction device, and a retraction device can also be usedas an insertion device. However, in some embodiments, a first device canbe used for insertion, and a second device can be used for retraction.The first device and the second device can be the same or substantiallythe same size, shape, etc. as each other, or be different in otherembodiments. In some embodiments, the device to be inserted or retractedhave a compressed or low-crossing profile configuration for delivery andremoval and an expanded configuration when implanted in the body. Insome embodiments, the device to be inserted or retracted has the sameconfiguration for both delivery, removal, and when implanted in thebody.

In some embodiments, the insertion and/or retraction device can beinterfaced with the implantable neural interface device to diagnosisand/or treat epilepsy, a movement disorder (e.g., Parkinson's Disease),a psychiatric disorder (e.g., clinical depression), the result of astroke, Alzheimer's disease, a cognitive disorder, an anxiety disorder,an eating disorder, an addition or craving, restless leg syndrome, asleep disorder, Tourette's syndrome, a stress disorder, coma, autism, ahearing disorder, a vision disorder, blindness, retinal degeneration,age related macular degeneration, cortical injury, optic nerve injury,dry eye syndrome, a speech disorder, amblyopia, headaches,temporomandibular joint disorder, pain (e.g., phantom limb pain andchronic pain), urinary incontinence, erectile dysfunction, bone disease,arthritis, tendonitis, the result of ligament or tendon damage, andparalysis (e.g., facial nerve paralysis and spinal paralysis). In someembodiments, the device system can be used to provide control of aprosthetic such as a limb or an external computer.

In some embodiments, the device system may wirelessly communicate with asystem that is connected to a network or cloud of data. In otherembodiments, the device system is connected to a biological interface tomonitor tissue. In some other embodiments, the device system isconnected to a biological interface to modulate tissue. In still otherembodiments, the device system is connected to a biological interface tomonitor and modulate tissue. In other embodiments, the biologicalinterface can include an implantable camera.

In other embodiments, the device system can insert and/or retract abiological interface to study, diagnose, and/or treat cardiovascularconditions such as heart failure, rheumatic heart disease, hypertensiveheart disease, ischemic heart disease, angina, coronary artery disease,cerebral vascular disease, stroke, atherosclerosis, cerebrovasculardisease, cardiomyopathy, pericardial disease, valvular heart disease,inflammatory heart disease, congenital heart disease, and peripheralarterial disease.

In still other embodiments, the device system can insert and/or retracta biological interface to study, diagnose, and/or treat cancers,including leukemia, lymphoma, myeloma, bladder cancer, lung cancer,brain cancer, melanoma, breast cancer, non-Hodgkin lymphoma, cervicalcancer, and ovarian cancer.

In other embodiments, the device system can insert and/or retract abiological interface to study, diagnose, and/or treat type 1 and type 2diabetes. In some embodiments, the device system can include abiological interface to study, diagnose, and/or treat orthopedicconditions, including osteoarthritis, rheumatoid arthritis, bonefractures, lower back pain, neck pain, and a herniated disk.

In other embodiments, the device system can insert and/or retract abiological interface to study, diagnose, and/or treat eye conditions,including glaucoma, cataracts, age-related macular degeneration,amblyopia, diabetic retinopathy, retinal detachment, retinal tearing,and dry eye syndrome.

In still other embodiments, the device system can insert and/or retracta biological interface to study, diagnose, and/or treat hearingconditions, including hearing loss, Meniere's disease, malformation ofthe inner ear, autoimmune inner ear disease, tinnitus, and vertigo.

In other embodiments, the device system can insert and/or retract abiological interface to study, diagnose, and/or treat tactile disorders,including impaired sensitivity to pressure applied to the skin, elevatedtwo-point discrimination thresholds (i.e. impaired spatial acuity), lossof vibratory sense, and deficits in proprioception.

In other embodiments, the device system can insert and/or retractbiological interface to study, diagnose, and/or treat taste, tasteimpairing conditions, smell, and smell impairing conditions.

In still other embodiments, the device system can be movably engagedwithin one, two, or more body tissues, regions, or organ systemsincluding but not limited to the scalp, skin, muscle, bone, neuraltissue, heart, lungs, trachea, bronchi, diaphragm, liver, pancreas,kidneys, bladder, urethra, spleen, esophagus, stomach, intestine, penis,testes, uterus, or ovary. In some embodiments, the insertion or removaltool need not necessarily be located within a body lumen, and can beused, for example, outside of a blood vessel such as an artery or thevein. In some embodiments, about or at least about 50%, 60%, 70%, 80%,90%, or more of a length of the insertion and/or removal tool is outsideof the body or a body lumen such as a blood vessel during the insertionor removal process.

In some embodiments, systems and methods as disclosed herein canmodulate neural tissue, and have a stimulatory or inhibitory effect.Neural tissue is specialized for the conduction of electrical impulsesthat convey information or instructions from one region of the body toanother. About 98% of neural tissue is concentrated in the brain andspinal cord, which are the control centers for the nervous system.Neurons transmit signals as electrical charges which affect their cellmembranes. A neuron has a cell body (soma) that contains a nucleus. Thestimulus that results in the production of an electrical impulse usuallyaffects the cell membrane of one of the dendrites, which then eventuallytravels along the length of an axon, which can be a meter long. Axonsare often called nerve fibers with each ending at a synaptic terminal.Neuroglia are cells of the CNS (central nervous system) and PNS(peripheral nervous system) that support and protect the neurons. Theyprovide the physical support for neural tissue by forming myelinsheaths, as well as maintaining the chemical composition of the tissuefluids and defending the tissue from infection. Schwann cells arespecialized PNS cells that form myelin sheaths around neurons. Neurons(nerve cell) include a cell body that contains the nucleus and regulatesthe functioning of the neuron. Neurons also include axons that arecellular process (extension) that carry impulses away from the cellbody. Neurons also include dendrites that are cellular process(extension) that carry impulses toward the cell body. A synapse is aspace between axon of one neuron and the dendrite or cell body of thenext neuron—transmits impulses from one neuron to the others.Neurotransmitters are chemicals released by axons and transmit impulsesacross synapses.

In some embodiments, provided is a closed loop control system forstimulating and monitoring neural activity. To meet this objective,microfilaments are embedded in various body configurations with sixdegrees of freedom to provide many system options for interacting withneural tissue. As an example, this would enable the data collected froma first recording microfilament (or external source) to help guide theoutput of a second stimulating microfilament.

The approximate diameter of circular microfilaments for conductingelectrical current is between 1 μm and 250 μm, such as no more thanabout 25 μm, 50 μm, or 75 μm. For electrical stimulation, larger sitesup to 50 μm would be advantageous to achieve surface areas that meetuseful stimulation current requirements without a coating. Theapproximate diameter of circular microfilaments for conducting ormonitoring light is between is 0.1 μm to 250 μm, such as no more thanabout 25 μm, 50 μm, or 75 μm. The approximate diameter of circularmicrofilament tubes for delivering or circulating gases, fluids, andmixtures in some embodiments is between 1 μm to 100 μm, or no more thanabout 50 μm, 75 μm, 100 μm, or 150 μm. Microfilaments can also be placedwithin a packed geometry that allows for a tapering of the penetratingarea cross sections to reduce the cross sectional area and thus longterm adverse neural tissue response. In some embodiments, themicrofilaments can extend outward from the body's surface; these sitescan be formed (e.g., bent or flattened) to provide desired functionalcharacteristics.

The array body can take multiple forms including penetrating structureswith microfilament sites and joining sections to optimize placementwithin the nervous system. An approximate cross sectional area of apenetrating array body in some embodiments is 1 μm² to 0.2 mm²,preferably up to approximately 7850 μm². For large area coverage as inelectrocorticography, larger body areas up to approximately 100 cm² ormore would be advantageous to collect more data from the outer surfaceof a neural tissue section. In some embodiments, insertion and/orretraction devices can be used to insert or remove neural interfacedevices such as those disclosed in U.S. Pat. No. 9,095,267 to Halpern etal., which is hereby incorporated by reference in its entirety.

The array body can also take on non-linear shapes, which allow novelinsertion techniques into difficult areas to access within surgery. Acurved shape can be rotated into position where a linear angle of attackis unavailable. The array body can also have a curve located atdifferent positions (e.g., proximal, midportion, or distal) to aid inanchoring to neural tissue or bone, while there may be a linear segmentdistal to, and/or proximal to the curved segment.

One advantage of the insertion and/or retraction device in someembodiments is the wide range of materials and components available toimprove insertion conditions and long term performance of a microscaledevice within a nervous system. The components of the device can beformed from, for example, one, two, or more of gold, platinum, platinumiridium, carbon, stainless steel, steel, titanium, niobium, aluminum,conductive polymers, polymers, ceramics, organic materials or any othermaterial depending on the desired clinical result.

A three-dimensional view of an example of an insertion and/or retractiondevice 50 is shown in FIG. 1. Some embodiments of the device 50 caninclude, for example, a tether 120, and a continuous body 105surrounding all or a portion of the tether 120. The continuous body canhave a width of, for example, between about 5 μm and 100 μm, or no morethan about 500 μm, 1000 μm, 1500 μm, 2000 μm, 2500 μm, 5000 μm, 7500 μm,or 10,000 μm. The continuous body can also have a length of betweenabout 1 mm and 10 mm, or no more than about 25 mm, 50 mm, 75 mm, 100 mm,or 200 mm. In some embodiments, the tether 120 includes an engagementhook 130 at one end for engagement with microscale devices. In stillother embodiments, an engagement loop could be positioned at one end,the tether can be integrally formed, or formed as part of a plurality ofbodies joined together, so long as it is physically continuouslyconnected together as a whole. In some embodiments, a device 50 couldinclude an adjustable hook that can be movable to create different sizedopenings for engagement. In still other embodiments, the distal end ofthe device 50 can be shaped to provide stiffness to a flexible or hingedmicroscale device. In some embodiments, the continuous body 105 can bean elongate tubular member, and/or be assembled to a robotic manipulatorthat adjusts position based upon the movement of the targeted tissue. Instill other embodiments, a control knob 180 with tracking pin feature182 or other feature such as a wheel, lever, or the like can, forexample, slide and rotate between the slot 184 communicating with ornear the proximal end of the device and the tension stop 186 that relaxand tension the tether 120 respectively. In some embodiments, theelasticity of the tether 120 allows for a degree of stretch sufficientfor the user to pull the control knob 180 back against before rotatingto a new position and allowing it to rest in a slot or track 184. Insome embodiments, the slot or track 110 and/or the slot or track 184 hasan axial length that is between about 1% and 50%, such as between about1% and 20%, or between about 1% and 10% of the axial length of thecontinuous body 105, or in some embodiments about or less than about50%, 40%, 30%, 20%, 10%, 5%, or less, or ranges encompassing any two ofthe foregoing percentages.

In other embodiments, a flap 140 can have a shape that is easier to grabby tweezers or other implements. In some other embodiments, the endeffector 130 can have an automated mechanism to grab a microscaledevice. In still other embodiments, near the distal end of thecontinuous body 105 can be shaped to engage with microscale devices ofdifferent shapes. In some other embodiments, the width of the endeffector can be between about 1 μm and 50 μm, or no more than about 100μm, 500 μm, 1000 μm, 1500 μm, 2000 μm, 2500 μm, 3000 μm, or 5000 μm. Instill other embodiments, the width of the opening of the end effectorcan be between about 1 μm and 50 μm, or no more than about 100 μm, 500μm, 1000 μm, 1500 μm, 2000 μm, 2500 μm, 3000 μm, or 5,000 μm. In otherembodiments, the width of an automated end effector can be between about1 μm and 50 μm, or no more than about 100 μm, 500 μm, 1000 μm, 1500 μm,2000 μm, 2500 μm, 3000 μm, or 5000 μm. In still other embodiments, thecontinuous body can be shaped to encourage the sliding of the tether 120when it is movably displaced. In some other embodiments, thecross-section of tether 120 can have a shape that prevents somerotations within the continuous body 105. In other embodiments, the endeffector can be any desired shape, including a shape that is threadedthrough an aperture on a micro-scale device. In still other embodiments,the tether can be elastic or inelastic. In some other embodiments, theaperture of the microscale device can be elastic or inelastic. In someembodiments, the tether has sufficient column strength to push thedevice to be inserted or removed distally. In other embodiments, anautomated or non-automated end effector can operably engage anddisengage with movable jaws, a movable clamp, a movable multi-headedhook, a movable anchor, a vacuum, a movable air nozzle, a movable cable,a movable loop, a movable net, a movable cup, a movable collet, amovable snake (e.g., an articulating flexible member, akin to a flexibleendoscope or device used to unclog pipes), a movable coil, a movablebarb, a movable snap-fit arm, a movable prong, a movable sheet, amovable strap, a movable threaded rod, a movable threaded hole, amovable anchor, a movable rod, a movable magnet, and a movable nozzlethat dispenses dissolvable material.

FIG. 1 shows an isometric view of an insertion device 50 with a tether120 housed within, and completely or partially encircled by thecontinuous body 105, which can be a tubular member within a centrallumen configured to house the tether 120 as shown. The distal end of thetether 120 can be looped around/tied to an aperture near the proximalend of the end effector 130 as shown. The flap 140 can extend radiallyoutwardly of a slot 110 extending proximally a distance from the distalend of the sidewall of the continuous tubular body 105. The proximal endof the tether 120 joined by a mechanical lock 122 to the control knob180 partially housed by the continuous body 105. The control knob 180has a tracking pin 182 that slides within track 184 extending distally adistance from the proximal end of the sidewall of the continuous tubularbody 105. The slot 110 can be circumferentially in line with, orcircumferentially offset from the slot or track 184 in some embodiments.The tracking pin 182 can be movably positioned to rest in tension stop186 to apply tension to tether 120.

FIG. 1A illustrates an isometric view of an insertion device 50 with atether 120 housed within, and encircled by the continuous body 105,which can be a tubular member within a central lumen configured to housethe tether 120 as shown. The distal end of the tether 120 can be loopedaround/tied to an aperture near the proximal end of the end effector 130as shown. The isometric view shows a tether 120 with wall thicknessesbetween about 1 μm and 25 μm, or no more than about 50 μm, 75 μm, 100μm, 150 μm, 250 μm, 500 μm, 1000 μm, or 2000 μm in some embodiments. Apair of tweezers 150, jaws, or other tool are guiding an end effector,e.g., engagement hook 130 by grasping a hook flap or tab 140, which canextend laterally from the body of the engagement hook 130 as shown, orat other desired locations. The flap 140 can extend radially outwardlyof a slot 110 extending proximally a distance from the distal end of thesidewall of the continuous tubular body 105. Beneath the insertiondevice distally is a microscale device 160 with shanks 164 extendingsubstantially orthogonal to a baseplate 161 and suspended by its cable162 above target tissue 170. The baseplate 161 has a loop 165 that canbe integral to the baseplate or joined to its surface.

FIG. 1B illustrates an isometric view of an insertion device with theend effector, e.g., engagement hook 130 engaged with a microscale device160 and tensioned against the distal end of a continuous body 105. Theengagement hook flap 140 extends radially outwardly of slot 110. Inother embodiments the end effector could take the form of a multi-headedhook, a magnet, a vacuum nozzle, a bayonet lock mechanism, a snap fitmechanism, a press fit, and a shape for threading through an aperture ona micro-scale device for example.

FIG. 1C illustrates an isometric view of the insertion device 50 of FIG.1 engaged with a microscale device 160 that has been inserted intotissue 170.

FIG. 1D illustrates an isometric view of the insertion device 50 of FIG.1 engaged with a microscale device 160 that has been inserted intotissue 170. Tweezers 150 grasping hook flap 140 are disengagingengagement hook 130 from a loop or other hook-engaging element on, e.g.,the proximal end of the microscale device 160 in preparation for removalof the insertion device 50.

FIG. 1E illustrates an isometric view of an insertion device 50retracted from, and disassociated with a microscale device 160 insertedin tissue 170. The steps illustrated in FIGS. 1B-1E could be performedin reverse order to retract a microscale device 160 previously insertedwithin tissue.

FIG. 2 illustrates a side view of the distal end of an insertion device200 above a microscale device 250 with an engagement loop 252 configuredto reversibly attach to an end effector of the insertion device. In someembodiments, the device 200 includes a pivotable engagement hook 230 anda guide rod 220 having a distal end connected to the pivotableengagement hook 230. The engagement hook 230 has fixed jaws as shown,although movable jaws are possible in other embodiments. In otherembodiments the engagement hook could take the form of, for example, afour bar linkage, a sliding component, grasping jaws, a multi-headedhook, a magnetic lock, a vacuum head, a bayonet lock mechanism, a snapfit mechanism, an actuated press fit, and an articulated snakingmechanism.

FIG. 2A illustrates a side view of the insertion device 200 of FIG. 2with a pivotable engagement hook 230 engaged with an engagement loop 252due to the displacement of guide rod 220.

FIG. 2B illustrates a side view of the insertion device 200 of FIG. 2with an engagement hook 230 on a pivot and engaged with an engagementloop 252. In some embodiments, a guide rod 220 has retracted an innerhousing 210, such as an inner tubular member, to tension a microscaledevice 250 against the distal end of the insertion device 200 (e.g., thedistal end of the continuous body outer housing). In some embodiments,the microscale device 250 could be flexible. In still other embodiments,the microscale device could include a single shank. In otherembodiments, the microscale device could be a device that emits energy,including light and/or magnetic fields.

FIG. 3 illustrates a side view of an insertion device 300 with a tethermember 310 encircled within a lumen of the continuous body 305. The sideview shows tether 310 with thicknesses between about 1 μm and 25 μm, orno more than about 50 μm, 75 μm, 100 μm, 150 μm, 250 μm, 500 μm, 1000μm, or 2000 μm in some embodiments. An end effector, e.g., engagementhook 320 is connected near its proximal end via an aperture or otherconnection to the distal end of the tether 310, such as via a loop inthe tether. The insertion device 300 is shown extended above amicroscale device 360 suspended by its cable 365. In some embodiments,microscale device 360 can be without a cable 365.

FIG. 3A illustrates a side view of the insertion device 300 of FIG. 3with a tether 310 encircled by, and the distal end of the tether 310 isextending distally with respect to the continuous body 305. The sideview shows a pair of tweezers 350, jaws, or other tool grasping a hookflap or tab 330 which can extend laterally from the body of theengagement hook 320 as shown, or at other desired locations and guide anengagement hook 320. The tool 350 can actuate the tab 330 in a desireddirection in order to move the engagement hook 320 in an appropriatedirection. Beneath the insertion device is a microscale device 360suspended by or otherwise attached to its cable 365. In someembodiments, the microscale device 360 has hinges 370 for flexibility.

FIG. 3B illustrates a side view of the insertion device 300 of FIG. 3with a tether 310 encircled by a continuous body 305. The side viewshows an engagement hook 320 inserted within engagement loop 380,aperture, or other complementary connector on the microscale device 360,such as on a proximal baseplate of the microscale device 360. A tether310 can tension the microscale device 360 against the distal end ofcontinuous body 305. In some embodiments, the distal end of thecontinuous body 305 engages the hinges 370 of the microscale device,stiffening the microscale device 360 for insertion into tissue. In stillother embodiments the distal end of the continuous body 305 has bossesthat insert into holes in a flexible microscale device. In otherembodiments, the insertion device mechanically stiffens the microscaledevice by engaging it from one or more sides. In still other embodimentsthe insertion device uses a vacuum or magnetic attraction to engage amicroscale device.

Although certain embodiments of the disclosure have been described indetail, certain variations and modifications will be apparent to thoseskilled in the art, including embodiments that do not provide all thefeatures and benefits described herein. It will be understood by thoseskilled in the art that the present disclosure extends beyond thespecifically disclosed embodiments to other alternative or additionalembodiments and/or uses and obvious modifications and equivalentsthereof. In addition, while a number of variations have been shown anddescribed in varying detail, other modifications, which are within thescope of the present disclosure, will be readily apparent to those ofskill in the art based upon this disclosure. It is also contemplatedthat various combinations or sub-combinations of the specific featuresand aspects of the embodiments may be made and still fall within thescope of the present disclosure. Accordingly, it should be understoodthat various features and aspects of the disclosed embodiments can becombined with or substituted for one another in order to form varyingmodes of the present disclosure. Thus, it is intended that the scope ofthe present disclosure herein disclosed should not be limited by theparticular disclosed embodiments described above. For all of theembodiments described above, the steps of any methods need not beperformed sequentially. The ranges disclosed herein also encompass anyand all overlap, sub-ranges, and combinations thereof. Language such as“up to,” “at least,” “greater than,” “less than,” “between,” and thelike includes the number recited. Numbers preceded by a term such as“approximately”, “about”, and “substantially” as used herein include therecited numbers (e.g., about 10%=10%), and also represent an amountclose to the stated amount that still performs a desired function orachieves a desired result. For example, the terms “approximately”,“about”, and “substantially” may refer to an amount that is within lessthan 10% of, within less than 5% of, within less than 1% of, within lessthan 0.1% of, and within less than 0.01% of the stated amount.

1-33. (canceled)
 34. A tool comprising: a housing; an elongate bodycomprising a proximal end and a distal end, the elongate body at leastpartially disposed within the housing; and an end effector operablycoupled to the distal end of the elongate body, the end effectorconfigured to reversibly couple or decouple with a portion of amicro-scale device, wherein the end effector is configured to be movedlaterally relative to the housing to facilitate coupling or decouplingwith the portion of the micro-scale device.
 35. The tool of claim 34,wherein the housing comprises a tubular body, a distal opening, and alateral slot.
 36. The tool of claim 35, wherein the end effector isconfigured to extend through the lateral slot.
 37. The tool of claim 35,wherein the lateral slot extends from a distal end of the tubular bodyof the housing.
 38. The tool of claim 34, wherein the end effectorcomprises a hook.
 39. The tool of claim 34, wherein the end effectorcomprises a laterally-extending tab configured to allow a user to movethe end effector laterally relative to the housing.
 40. The tool ofclaim 34, wherein the end effector is configured to pivot relative tothe housing.
 41. The tool of claim 34, wherein the end effector isconfigured to be skewed relative to a longitudinal axis of the housing.42. The tool of claim 34, further comprising a control knob configuredto actuate the elongate body proximally or distally with respect to thehousing.
 43. A method comprising: providing a tool comprising: ahousing; an elongate body comprising a proximal end and a distal end,the elongate body at least partially disposed within the housing; and anend effector operably coupled to the distal end of the elongate body;and reversibly coupling or decoupling the end effector with a portion ofa micro-scale device, wherein the end effector is configured to be movedlaterally relative to the housing to facilitate coupling or decouplingwith the portion of the micro-scale device.
 44. The method of claim 43,wherein the micro-scale device comprises a neural interface.
 45. Themethod of claim 43, wherein the micro-scale device comprises abiological interface.
 46. The method of claim 43, wherein reversiblycoupling or decoupling the end effector with the portion of themicro-scale device does not substantially displace the micro-scaledevice.
 47. The method of claim 43, further comprising monitoring themotion of a target surface.
 48. The method of claim 47, furthercomprising positioning the micro-scale device and adjusting thepositioning speed as a function of the monitored motion of the targetsurface.
 49. The method of claim 43, further comprising manipulating alaterally-extending tab of the end effector.
 50. The method of claim 43,further comprising inserting the micro-scale device by pushing themicro-scale device with the elongate body.
 51. The method of claim 43,further comprising positioning the micro-scale device at a targetlocation before decoupling the end effector with the portion of themicro-scale device.
 52. The method of claim 43, further comprisingwithdrawing the insertion tool after insertion of the micro-scale deviceat a target location.
 53. The method of claim 43, further comprisingwithdrawing the insertion tool and the micro-scale device.